Fluorosed dental enamel is caused by the ingestion of above optimal levels of fluoride. Clinically, mild enamel fluorosis appears as white opacities on the teeth, while severe fluorosis results in pitting and loss of surface enamel. These fluorotic teeth are prone to fracture and show abnormal wear patterns which lead to difficult problems in restoration. Fluorosed enamel is characterized by an increase in the content of organic material and a decrease in the mineral. This may be due to a direct effect on the ameloblasts and/or a direct effect on the enamel. The purpose of this proposal is to investigate the effects of the ingestion of chronic high levels of fluoride in drinking water on enamel formation and the mechanisms by which fluorosis occurs. The specific aims include the following: To determine the effects of chronic, high levels of fluoride in the drinking water: (1) on the two classes of proteins in developing enamel; (2) on the cyclic modulation of the maturation ameloblasts as reflected by the staining of the enamel for free and loosely bound calcium; (3) on the morphology of the enamel organ; and (4) to determine the reversibility of the effects of the ingestion of chronic high levels of fluoride in the drinking water on enamel and on the enamel organ. Fluorosed and control enamel proteins will be compared by molecular weight and by amino acid analysis. The modulation of the maturation ameloblasts will be compared histologically using SEM and indirectly by calcein staining of the periodic stripes in maturation enamel. Changes which occur in fluorosed enamel will be compared to the changes which occur in the fluorosed enamel organ. These studies will show when in enamel development high levels of fluoride exert their effect and on which components this effect is manifest, and will lead to further understanding of the mechanisms involved in formation of fluorotic enamel.